Fragmentomics features of cell free DNA in eating disorders

Eating disorders are lacking reliable biomarkers despite their severe psychiatric and medical burden. In this study, we examined plasma cell-free DNA (cfDNA) from patients with the restrictive (ANR), or binge-purge (ANBP) subtypes of anorexia nervosa, as well as from those with bulimia nervosa (BN), and controls, using the BIABooster electrophoresis method and shallow whole-genome sequencing to characterize cfDNA fragmentomics. While absolute cfDNA concentrations did not differ between groups, patients exhibited consistent qualitative alterations. Patients with BN showed increased cfDNA at the first nucleosomal peak, while all patient groups displayed shifts towards shorter fragments in the second and third nucleosomal peaks. End-motif analysis revealed higher motif diversity and trinucleotide sequence motifs TNN-type enrichment in ANR, together with a lower ratio of trinucleotide sequence motifs CGN to NCG, which has been correlated with hypomethylation. Multivariate analyses demonstrated that ANBP exhibits a distinct molecular profile that is not explained by combined effects of anorexia and bulimia. These findings suggest that cfDNA in eating disorders carries biologically meaningful signatures related to chromatin organization, nuclease activity, and methylation. This supports the potential of cfDNA as a minimally invasive biomarker for the clinical management of eating disorders.